The high per patient cost of quantitative, high-sensitivity molecular diagnostics is one of the key roadblocks limiting the transition of this technology from the clinical laboratory to point-of-care diagnostics in low-to-middle income countries (LMICs). As a solution, we present a low-cost system architecture for fluorescence-based point-of-care diagnostics using small volume patient sera samples. Our approach combines an inexpensive 4-site microscope slide reader with low per patient cost consumables using conventional glass microscope slides, pre-printed with biorecognition molecules. We use a neuromorphic-inspired, charge-integrating readout circuit architecture combined with optical filters in a sandwich-style configuration to achieve high-sensitivity while trading off detection time and number of biorecognition sites per slide. Our demonstrated lower limit of detection using Nile Red fluorescent microspheres was a 1,000,000:1 dilution corresponding to approximately 200 microspheres per detection site, approaching the sensitivity of a conventional high-cost desktop clinical laboratory microscope slide reader.